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11 February 2012
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| [ Print-friendly version ] |
| A phase III, randomised, multicentre, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa-2a with Child's A or B cirrhosis in Chronic Hepatitis C virus infection |
| ISRCTN | ISRCTN88008850 |
| ClinicalTrials.gov identifier | |
| Public title | A phase III, randomised, multicentre, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa-2a with Child's A or B cirrhosis in Chronic Hepatitis C virus infection |
| Scientific title | |
| Acronym | PACIFIC |
| Serial number at source | RHM MED 0560/ML17066 |
| Study hypothesis | To investigate the incidence of mortality and morbidity amongst patients with cirrhosis (Child-Pugh Grade A and B) due to chronic hepatitis C treated with Pegylated Interferon (PEG-IFN). |
| Lay summary | |
| Ethics approval | Not provided at time of registration |
| Study design | Randomised controlled trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Liver cirrhosis in Hepatitis C Virus infections. |
| Participants - inclusion criteria |
To be eligible for this trial, patients must have documentation of the following:
1. Aged over 18 years 2. Serologic evidence of Hepatitis C Virus (HCV) infection by an anti-HCV antibody test 3. Qualitative evidence of infection with HCV Ribonucleic Acid (RNA) 4. Chronic liver disease consistent with chronic hepatitis C infection on a biopsy as judged by a local pathologist 5. Patients must have had an abdominal ultrasound, Computed Tomography (CT) scan, or Magnetic Resonance Imaging (MRI) scan with evidence of cirrhosis, but without evidence of hepatocellular carcinoma (within two months of randomisation) and a serum alphafetoprotein (AFP) less than 100 ng/ml. Patients with elevated AFP should have evidence of no increase of more than 10 KIU/l for three months prior to entry 6. Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all fertile male patients, male patients with female partners of childbearing age, and females must be using two reliable forms of effective contraception during the study |
| Participants - exclusion criteria |
Patients with any of the following will not be eligible for participation:
1. Patients who are expected to need systemic antiviral therapy at any time during their participation in the study are excluded. Exception: patients who have had a limited (seven day) course of acyclovir or alcyclovir for herpetic lesions more than one month prior to the first administration of test drug are not excluded 2. Positive test at screening for anti-Hepatitis A Virus (anti-HAV) Immunoglobulin M (IgM) antibody (Ab), Hepatitis B surface Antigen (HBsAg), anti-Hepatitis B core (anti-HBc) IgM Ab, or anti-Human Immunodeficiency Virus (anti-HIV) Ab 3. Documented serum concentrations of ceruloplasmin or a1-antitrypsin consistent with an increased risk of metabolic liver disease 4. History or other evidence of a medical condition associated with chronic liver disease (e.g. hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures) 5. Women with ongoing pregnancy or breast feeding 6. Decompensated liver disease within the last three months 7. Neutrophil count less than 1500 cells/mm^3, Hgb less than 12 g/dl in women or 13 g/dl in men, or platelet count less than 60,000 cells/mm^3 8. Any patient with a baseline increased risk for anemia (e.g. thalassemia, spherocytosis, history of gastrointestinal [GI] bleeding etc.) or for whom anemia would be medically problematic 9. Serum creatinine level more than 1.5 times the upper limit of normal at screening 10. Patients unlikely to comply with the study schedule due to alcohol and/or drug abuse 11. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least three months at any previous time or any history of the following: a suicidal attempt, hospitalisation for psychiatric disease, or a period of disability due to a psychiatric disease 12. History of immunologically mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management etc.) 13. History or other evidence of chronic pulmonary disease associated with functional limitation 14. History of a severe seizure disorder or current anticonvulsant use 15. Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is more than 20% within two years. Patients with a lesion suspicious for hepatic malignancy on the screening imaging study will only be eligible if the likelihood of carcinoma is less than 10% following an appropriate evaluation 16. History of having received any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) less than six months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study 17. History of major organ transplantation with an existing functional graft 18. History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded 19. History or other evidence of severe retinopathy 20. Inability or unwillingness to provide informed consent or abide by the requirements of the study 21. History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study |
| Anticipated start date | 01/04/2004 |
| Anticipated end date | 01/04/2007 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 100 total - 50 treatment arm, 50 conventional management arm |
| Interventions |
Intervention: PEG-IFN - 90 mg subcutaneously (sc) once weekly for one month, 135 mg sc once weekly for one month, rising to 180 mg thereafter as tolerated in 1 ml solution administered sc once weekly for a total of 48 weeks.
Control: conventional management. |
| Primary outcome measure(s) |
1. Combined endpoint of non-detectable serum HCV-RNA (less than 100 copies/ml by the AMPLICORä Polymerase Chain Reaction [PCR] assay) at the end of the 24 week treatment-free follow-up period
2. Death 3. Liver transplantation (or need for) 4. Hepatocellular cancer |
| Secondary outcome measure(s) |
1. End-of-treatment virological and biochemical responses
2. Bleeding varices 3. Ascites 4. Spontaneous bacterial peritonitis and other infections 5. Encephalopathy 6. Quality of life as measured by the SF 36 and Fatigue Severity Scale |
| Sources of funding |
Peginterferon supplied free of charge from Roche Pharmaceuticals.
Investigator-led study, funded from Southampton NHS R&D Levy. |
| Trial website | |
| Publications | |
| Contact name | Prof William Rosenberg |
| Address |
Professor of Hepatology
Level D MP811 Southampton General Hospital |
| City/town | Southampton |
| Zip/Postcode | SO16 6YD |
| Country | United Kingdom |
| Tel | +44 (0)23 80798945 |
| wmr@soton.ac.uk | |
| Sponsor | Southampton University Hospitals NHS Trust (UK) |
| Address |
Southampton General Hospital
Tremona Road |
| City/town | Southampton |
| Zip/Postcode | SO16 6YD |
| Country | United Kingdom |
| Tel | +44 (0)23 80777222 |
| wmr@soton.ac.uk | |
| Date applied | 20/07/2005 |
| Last edited | 16/12/2010 |
| Date ISRCTN assigned | 25/10/2005 |
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| © 2012 ISRCTN unless otherwise stated. | |
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